The classical concept of the cortical control of sequential movements is that the premotor areas, particularly those on the medial wall of the hemisphere, are critical for learning and storing the representations of new sequences. According to this view, the primary motor cortex (M1) is thought simply to produce the patterns of muscle activity necessary to implement the plans generated by the premotor areas. Recent data have led to some challenges to this point of view, and raise the possibility that M1 plays a more active role in the acquisition and retention of sequential movements than previously thought. The primary goal of this project is to examine whether practicing sequences of movements actually induces changes in the response properties of M1 neurons, as well as induces changes in the properties of neurons in the premotor areas that project to MI. In preliminary studies, we developed a behavioral task that allows us to examine the processes of motor skill acquisition, performance and retention in monkeys. Next, we recorded the activity of neurons in the arm area of M1 in one monkey that was over-trained to perform sequences of pointing movements- internally generated or visually instructed. Our initial results suggest that, with practice, aspects of learned sequences come to be represented in the activity of M1 neurons. We also used the 14C-2-deoxy-glucose (2DG) technique to image metabolic activity associated with performance of the internally generated movement sequences. The imaging results provide further evidence that long-term practice on sequences alters activity patterns in MI. To further explore the cortical control of sequential movements, we propose to continue our examination of the effects of extended practice on the response properties of M1 neurons and on the patterns of metabolic labeling in MI. Next, we will compare the response properties of M1 neurons with those of neurons in several premotor areas in the frontal lobe that project to it. Finally, we will examine the activity of M1 neurons in monkeys who are at early, middle and late stages of skill acquisition.